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The HYAFF® scaffold for one-step cartilage repair with MSCs

HYALOFAST® is based on Anika’s proprietary HYAFF® technology which involves the chemical modification of hyaluronan (HA). Hyaluronic acid (HA) is a major component in chondrocytes extracellular matrix (ECM) organization and it is a chondroinductive factor responsible for modulating pericellular matrix before cell condensation. Moreover, HA is the main component of synovial fluid and acts as a lubricating and a shock absorbing molecule inside the joint. Thanks to the HYAFF® technology, fully biocompatible and biodegradable 3D scaffolds have been created.  These are suitable for in-situ attachment and differentiation of the undifferentiated mesenchymal cells present in the subchondral compartment after their mobilization via microfracture and/or perforation procedures, or of autologous bone marrow aspirate. This is as per the concept of guided regeneration of tissues.

HA is the main component of synovial fluid and acts as a lubricating and a shock absorbing molecule inside the joint. In addition, it ensures the proper 3D configuration of the hyaline cartilage ECM.

HA has been used for more than 25 years as a synovial fluid replacement and visco-supplement agent for treatment of osteoarthritic pain . It is also one of the most critical components for the maintenance of the physico-chemical properties of hyaline cartilage, a unique avascular tissue which, once damaged, cannot spontaneously regenerate. In fact, damaged hyaline cartilage is normally replaced by fibrous cartilage, a repair tissue which cannot sustain the same level of mechanical stress as hyaline cartilage. This sometimes seriously limits the patient’s level of physical activity, in particular for younger people or people practicing sports. HA has also been shown to participate to the control of morphogenesis, cell differentiation, cell division and signal transduction into the cell’s nucleus of progenitor cells, while high HA levels are responsible for the so-called fetal scarless repair (typical of cartilage and cutaneous tissues) during an embryo’s development. Therefore, a synthetic matrix based on HA can mimic the embryonic hyaluronic acid-rich environment supportive for MSCs recruitment and differentiation along the osteogenic and chondrogenic lineages in the adult organism.

Mesenchymal Stem cells (MSCs) are pluripotent, self-renewing cells capable of generating all major skeletal tissues, when grown in appropriate environment, therefore representing a promising approach for tissue restoration in regenerative medicine.

The use of MSCs is clinically appealing as the possibility of aspirating bone marrow directly during the surgical procedure or recruiting MSCs at the defect site via microfracture or perforation techniques, are one-step procedures. For the success of both these approaches, it is necessary to guarantee that bone-marrow MSCs are maintained in situ, preferably in an environment which is conducive to differentiation, after direct mobilization or application of the bone marrow aspirate, avoiding cell dispersion in the articular space and promoting tissue regeneration.

A breakthrough in medical science was the introduction of a chemically-modified HA derivative, known as HYAFF11® which is the benzyl ester of HA.

HYAFF11® polymers are water-insoluble and, therefore, can be manufactured in many different 3D configurations including non-woven scaffolds of HYAFF® fibres, sponges, granules and membranes. The uniqueness of HYAFF® is found in its prolonged residence time in-situ compared to native HA and the fact that, upon spontaneous degradation at the implant site, HYAFF®’s main by-product is the parental HA molecule. This provides a unique biocompatibility profile to HYAFF® biomaterials and leads to an HA enriched environment at the implant site. It is believed that such a HA-rich environment can promote the recapitulation of the embryonic events and thereby facilitate tissue repair in the adult organism. HYAFF® fibers in a non-woven configuration have been proven to be an optimal scaffold for in-vitro MSC differentiation along the chondrogenic or osteogenic pathway.

HYALOFAST® has been developed to support MSCs engraftment for the treatment of chondral and osteochondral lesions.

In fact, in parallel to its bio-resorption, the remodeling of the chondral and osteochondral tissue is promoted, thanks to the unique inductive role of the HYAFF® scaffold. HYALOFAST® is a user-friendly matrix, that can be applied with mini-invasive procedures, such as arthroscopy or mini-arthrotomy. It acts as a biological biodegradable prosthesis which guides tissue remodeling and the healing of both the bone and cartilage tissues through the action of the MSCs, which have populated the scaffold.

References

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  • Chen W.Y.J., Abatangelo G. Functions of hyaluronan in wound repair. Wound Rep and Regen 1999;(7): 79-89
  • Zavan B., Giorgi C., Bagnara G.P. Vindigni V., Abatangelo G., Cortivo R. Osteogenic and chondrogenic differentiation: comparison of human and rat bone marrow mesenchymal stem cells cultured into polymeric scaffolds. Eur J Hystochem 2007; 51(1): 1-8

The HYALOFAST® scaffold
Scanning electron micrograph of Hyalofast®: 10 micron in diameter HYAFF® fibers are shown. Fibers are randomly organized in the non-woven structure (magnification: 1,300x).